2016 Research Grant Recipient: Dr. Sindu Kanjeekal

Identifying a genetic signature that predicts progression of non-invasive urothelial (bladder) carcinoma to an invasive cancer

SUMMARY OF RESEARCH PROJECT

Bladder cancer is the 5th most common cancer in Canada, with an estimated 8,300 Canadians diagnosed each year. The most common presenting symptom of bladder cancer is painless blood in the urine. If an abnormality is found in the bladder, a

biopsy is taken to determine if cancer is present. The pathologist must then determine whether the cancer cells are 1) limited to the superficial layer of the bladder wall called the urothelium (stage Ta), 2) have invaded the next tissue layer called the lamina propria (stage T1), 3) have invaded into the inner muscle layer (stages T2-T3), or 3) have penetrated through the bladder wall (stage T4). Cases where the cancers cells are limited to the urothelium or the lamina propria (stages Ta and T1) are considered non-muscle invasive bladder cancer, whereas, stages T2-T4, are referred to as muscle invasive bl

adder cancer. Metastatic disease, which is incurable, occurs when cancer cells that have spread to other organs.The majority of patients are diagnosed with non-muscle invasive bladder cancer and do not require surgical removal of the bladder. Low-grade non-muscle invasive disease is generally treated

with local measures. Although it does recur frequently in the bladder thus requiring life-long cystoscopic surveillance, recurrence typically does not progress to more dangerous systemic disease. On the other hand, high-grade non-muscle invasive disease and carcinoma in situ do recur locally, and in

approximately 25% of cases, progresses to muscle invasive bladder cancer. In some cases, they progress directly to metastatic disease. Patients with muscle invasive bladder cancer are usually recommended radical cystectomy (surgical removal of entire bladder) or radiation plus chemotherapy.Despite these aggressive measures, patients with muscle invasive bladder cancer are at a high risk of death because of relapse with metastatic disease. This key transition from high-grade non-muscle invasive disease to muscle invasive disease is poor

ly understood. As a result, it is a tremendous challenge for physicians to predict which cases will progress to advanced muscle invasive cancer that will require surgical removal of the bladder, or worse become an incurable metastatic disease.

HOW THIS RESEARCH HELPS ADVANCE QUALITY CANCER CARE IN OUR COMMUNITY

The primary objective of this research proposal is to examine tumour specimens from patients diagnosed high grade non-muscle invasive bladder cancer and determine if there is a molecular profile that will predict which patients are at greatest risk of progression to muscle invasive or metastatic disease. This molecular signature will be critical in identifying the most efficacious treatment strategies for bladder cancer patients. It will also identify a group of at-risk patients whom may benefit from novel clinical trials using targeted chemotherapies and immunotherapies, strategies consistent with Cancer Care Ontario’s priority on personalized medicine for cancer care. It is also significant that the proposed research brings together a multidisciplinary team of four clinicians and surgeons from Windsor Regional Hospital and four researchers from the Department of Biological Sciences and the School of Computer Science at the University of Windsor contributing a wide-range of expertise to better understand the progression of high-risk bladder cancer.

Click here for a PDF version of this Seeds4Hope Research Grant Summary.